Coronary angiographic findings and troponin T in patients with unstable angina pectoris.

This study sought to identify differences in coronary anatomic pathology in patients with unstable angina and elevated versus nonelevated serum troponin T values. Previous studies have shown a worse prognosis in unstable angina patients with elevated serum troponin T values. Consecutive patients (n = 117) with Braunwald class IIIB angina were included in the study. Serum samples for troponin T were obtained at admission and every 6 to 8 hours for 18 to 24 hours. Acute myocardial infarction was excluded by routine creatine kinase measurements. All patients underwent coronary angiography before discharge. Cardiac events including cardiac death and myocardial infarction were recorded. Two thirds of the patients with unstable angina had no increase in serum troponin T (<0.1 microg/L) (n = 80). They had a lower incidence of 3-vessel disease (26% vs 46%, p <0.001), left main disease (5% vs 16%, p = 0.04), visible thrombus (4% vs 22%, p = 0.006), and less severe stenosis of the culprit artery (65% vs 84%, p <0.004) than patients with elevated serum troponin T values (> or =0.1 microg/L) (n = 37). The 1-year cardiac event rate was 0% versus 19% in patients with troponin T values <0.1 microg/L compared with patients with serum troponin T values > or =0.1 microg/L (p <0.0001). It was concluded that patients with unstable angina and no release of troponin T have less severe coronary artery disease, and have an excellent prognosis. It is suggested that these patients may be managed more conservatively and without invasive evaluation before discharge.

[Serum myoglobin as a non-invasive marker of coronary reperfusion after intravenous thrombolytic therapy in patients with acute myocardial infarction]. / Serummyoglobin som ikkeinvasiv markør for koronar reperfusion efter intravenøs trombolysebehandling hos patienter med akut myokardieinfarkt.

Non-invasive methods for evaluation of intravenous thrombolytic treatment in patients with acute myocardial infarction (AMI) are needed, since approximately 30% of the patients never obtain coronary reperfusion. These patients could be candidates for additional thrombolytic treatment or acute PTCA. This study included 63 AMI patients. Intravenous and/or intracoronary thrombolysis was given to 52 patients, and 11 patients received conservative treatment (placebo). Serum myoglobin was measured every 15 min. Acute coronary angiography showed a patent coronary artery in 49 patients ("Reperfusion" group), and 14 patients had no coronary reperfusion ("No-Reperfusion" group). Mean time to peak serum myoglobin was 149 (57-194) minutes in the "Reperfusion" group and 476 (330-660) minutes in the "No-Reperfusion" group, p < 0.0001. An observed peak serum myoglobin < 5 hrs. after initiation of intravenous thrombolysis would indicate coronary reperfusion with sensitivity = 0.94; specificity = 0.79; predictive values of positive and negative test: 0.94 and 0.79, respectively. It is concluded that an peak serum myoglobin < five hrs. after start of thrombolysis predicts reperfusion status with a high level of accuracy.

[Serum creatine kinase isoenzyme MB and myoglobin in patients with acute myocardial infarction and coronary reperfusion]. / Serum-kreatinkinase isoenzym-MB og -myoglobin hos patienter med akut myokardieinfarkt og koronar reperfusion.

Thrombolytic therapy in patients with acute myocardial infarction (AMI) changes the time-concentration curve of serum creatine kinase isoenzyme MB (CK-MB) and serum myoglobin. In this study, 60 AMI patients received thrombolytic therapy and acute coronary arteriography, or conservative treatment. Group one (n = 32) demonstrated a patent infarct-related artery after intravenous thrombolytic therapy; group two (n = 17) had an initially occluded coronary artery which became patent during catheterisation; group three (n = 11) did not receive thrombolytic therapy. Frequent serum CK-MB and myoglobin measurements showed that patients with acute coronary reperfusion had a rapid increase, an earlier peak value and less total release of both CK-MB and myoglobin to blood compared to AMI patients treated conservatively. The changes in serum myoglobin compared to CK-MB demonstrated an even more rapid, more uniform, and relatively greater increase. Measurements of serum myoglobin may be a useful non-invasive method for evaluation of thrombolytic therapy in AMI patients.

Very early diagnosis and risk stratification of patients admitted with suspected acute myocardial infarction by the combined evaluation of a single serum value of cardiac troponin-T, myoglobin, and creatine kinase MB(mass)

AIMS: The diagnostic and prognostic capacity of biochemical markers of acute myocardial infarction in the emergency department were evaluated in consecutive patients (n=155) with suspected acute myocardial infarction. METHODS AND RESULTS: Serum myoglobin >/=110 microg. l(-1)and creatine kinase MB(mass)>/=5 microg. l(-1)had a high accuracy (0.77-0.85) (ns) for acute myocardial infarction diagnosis in patients presenting >2 h after symptom onset. Troponin-T (>/=0.10 microg. l(-1)) had a lower accuracy (0.53-0.70) for acute myocardial infarction diagnosis, but was the most important 1-year prognostic marker (cardiac death or non-fatal acute myocardial infarction). In patients without ST elevation, combined analysis of two biochemical tests would accurately identify an additional 20% of acute myocardial infarction patients (predictive value of a positive test=0.82) and also identify those without acute myocardial infarction (predictive value of a negative test=0.80). One-year event-free survival was excellent (96%) for patients with two negative biochemical tests, intermediate (74%) for those with discordant tests, and only 53% for patients with two positive biochemical tests. CONCLUSIONS: Analysis of biochemical tests in the emergency department prior to hospital admission could accurately identify approximately 20% additional acute myocardial infarction patients. The prognosis of these patients is poor, and they may be a target for primary PTCA or new early initiated aggressive medical therapies.

Serum myoglobin for the early non-invasive detection of coronary reperfusion in patients with acute myocardial infarction.

The ideal non-invasive method for detecting coronary reperfusion has not yet been established. In 63 patients with acute myocardial infarction, serum myoglobin and creatine kinase-MB were measured every 15 min. Thrombolytic treatment was given (n = 52) and acute coronary angiography showed a patent infarct-related artery in 49 patients while 14 patients had no coronary reperfusion. Median time to peak serum myoglobin was shorter (reperfusion group 178 min vs no reperfusion group 480 min, P < 0.0001) than time to peak serum creatine kinase-MB (reperfusion group 550 min vs no reperfusion group 1080 min, P < 0.0001), P < 0.0001. Myoglobin appearance rate, calculated as the concentration at 2 h divided by baseline values (Mb2/Mb0) was highest in the reperfusion group (4.0 vs 1.6), P < 0.001. An earlier proposed index, Mb2/Mb0 > 2.4 for identification of reperfusion 2 h after thrombolytic therapy, showed predictive values of positive and negative tests of 0.94 and 0.44, respectively. Combining this index with signs of medium to larger infarct size (Mb2 > 200 micrograms.l-1) increased the predictive value of the negative test to 1.00. In patients with signs of minor infarcts (Mb2 < 200 micrograms.l-1) the predictive values of positive and negative tests were 0.94 and 0.79, respectively, 5 h after onset of thrombolytic therapy. An early rise and a peak in serum myoglobin values seems to be a reliable and simple non-invasive indicator of successful and unsuccessful reperfusion therapy.

Recombinant activated factor VII (rFVIIa): characterization, manufacturing, and clinical development.

Recombinant activated coagulation factor VII (rFVIIa) (NovoSeven) was developed for treatment of bleeding in hemophilia patients with inhibitors (antibodies) against factors VIII or IX. rFVIIa initiates the coagulation cascade by binding to tissue factor at the site of injury and causes the formation of sufficient amounts of thrombin to trigger coagulation. Patients with a variety of other coagulation deficiencies than hemophilia characterized by an impaired thrombin generation and life-threatening bleeding have been reported as successfully treated with rFVIIa. Data are now entered into clinical registries established to further monitor this experimental treatment with NovoSeven. rFVIIa is produced free of any added human protein. The amino acid sequence of rFVIIa is identical to plasma-derived FVIIa (pdFVIIa). Posttranslational modifications (i.e., gamma-carboxylations, N- and O-glycosylations) are qualitatively identical in pdFVIIa and rFVIIa although some quantitative differences exist. The activities of rFVIIa and pdFVIIa are indistinguishable. Manufacturing of rFVIIa involves expression in baby hamster kidney (BHK) cells followed by purification, including three ion-exchange and one immunoaffinity chromatography steps. The last anion-exchange chromatography step ensures completion of the autoactivation of recombinant factor VII (rFVII) to rFVIIa. This review describes the mechanism of action, characterization, manufacturing, and preclinical and current clinical evidence for the efficacy and safety of rFVIIa.